Preparation of acyloxymethyl oxazolines



Patented Apr. 25, 1950 UNITED OFF-ICE PREPARATION' OF "'OXAZOLINES Philip F; Tryon, Terre Haute,: Ind; assignorr-to Commercial solvents Corporatiom-TeneHauta: lxi'd amorporationof Maryland .1 .NoTDravving. Application septenibeflilf i944;

' This invention relates to a method -for prepay in'g esters' ofhydroxymethyl -2*-oxazolines in high yieldsg and more. particularly to a method for preparingwompounds having the followingistruciture v omooom .inwhich the .R1 .substituents are the same and may be=ally1-or'aryl, and R may be hydrogen, .alkyl "or acyloxym'ethyl.

Esters of 'hydroxymethyloxazolines areknow and my copendingapplication,:seria1 No.'-482,W58,

filed Apr-il -12, -1943 ,-now-U. S. Patent 2,372,409,

describes a- --method 'for their preparation' i from esters of nitro hydroxy compounds. However. yields of hydroxymethyl oxaaoline esters prepared accordingitothis method arelow, and the ..process-, aceordingly; is expensive.

Lhave nowfound, that --esters of hydroxy methyl oxazolines can-betprepared in-high yields off-the ordervv of 60-9Q% from primary amines, .polyhydroxy. compounds and monocarboxylic .or-

.ganic acids, accordineto thesehemeillustrated helow lin whichallthesteps are caused to take place "in a Single operation.

. Serial No. 553;671

' '6 Claims. (Cl.-260+307) 2 of resulting ester are v.lovvl, in the neighborhood of only about 20-60%.

I rh'ave 'found, however, i that "if. rsufilcient acid is added initially both to formthehydroxymethyl oxa'zoline and to esterifythe other hydroxyl grou'p or groups, high yields of the order of 60-90% based on the aminohydroxy compound used are -obtaine'd and us'ually between 80 and 90%.

in which Rniay be'hydrogen, alk'yl, for hydro'iiye 'methyl. Among compoundsof this type may be mentioned 2 .-amino-"l,3-propanediol, 'f2-amino-i 2- methyl-lQB-p'ropanedi'dl; 2-an'1ino 2 ethyl-1.3- propanedioli tris (hydroXymethyD aminomethane, and the like.

'Some of the compounds WIh'ichcan be prepared accordance with my invention are'2-pheny1- 4 methyl 4QbenZoiixymethy1-2-oxazoline; 2-hepityll-methyl-4-octanooxymethyl 2 oxazoline; 2' nony1-4-methyl-4-decano'6xyniethyl-2-oxazoline; "2,4 di'th ylA-propionoxymethyl-2-oxa2oline; 2 nony1-"4-ethyl-4 decano6xymethyl 2-okazoline; 2-propy1 4,4 bis(butyroxymethyl)-2- oxazoline; 2 pentyle lA-bis(hexanooxymethyl) 2'-oxazoline; 2-heptyl-4A-bis (octanooxymethyl) V 2'-oxa2oline; 2-heptadecyl-4,4-bis(stearoxymeth- In the above scheme R"may"be hydrogen, alk'ylj;

may be hydrogen, alkyl; aracyioxymethyl.

If, in "the "abovesch'enie, steps Ifand II are carried out independently of stepjIII, itl-iair= is, only a single mole of orga'ni'c acid is used-so that.

the hydroxym'ethyl .oxazoline is .firs't .produced,

and then the hydroxymethyl group is subsequent- 1y esterified in a separate operation, the yields yl) -2-0xazoline; 2 phenyl-4-benzo6xymethy1-2- oxazoline; 2-.eth-yl-4epropionoxymethyl-2-oxazoline; i 2-'undecyl-4-lauroxymethyl 2 oxazoline,

and thelike: v

In practicing" my invention I mix the primary "amine polyhyd'rdxy com ound with the ap ropl'iate monecarboayiie organicacid in theQlatio of one mole :of primary. amine I polyhydroxy com pound to twoor more moles of theorganic acid,

depending on and corresponding to thesnumber of hydroxyl groups of the amine. Sometimes a slight excess of acid over the indicated equivalent quantities may be employed to bring the reaction more rapidly to completion, but yields are usually excellent with no excess of either component. The mixture is then heated over an increasing temperature range of about 150 C. to 240 C. with means for removing and collecting the water of reaction, until approximately the theoretical amount of water has been removed to indicate substantially complete conversion to the desired product, that is, two molecular equivalents of water will separate in oxazoline formation, and one additional molecular equivalent for each hydroxyl group esterified, the time for the total reaction usually being a period of about 6 to hours. The reaction products may then be purified by distillation if liquids, or crystallization if solids.

In order to further illustrate the process of my invention, the following examples are given.

EXAMPLE I The compounds listed below in Table I were prepared by the following procedure: 1 mole of 2-amino-2-methyl-1,3-propanediol was mixed 4 EXAMPLE II The compounds listed in Table II below were prepared by mixing in each case 1 mole of 2 amino-Z-ethyl-1,3-propanediol with 2 moles of the organic acid listed in the table in a reaction vessel equipped with a 3"x all-glass helix packed column fitted with a decanter or separator adapted to separate two liquid layers. Benzene was added to the decanter and allowed to overflow and fill the column and just begin to drop into the reaction vessel. The mixture was heated for a period of about 10 hours over an increasing temperature range of 150 to 240 C., during which time the water of reaction was removed as an azeotrope with the benzene in the column. The water was separated in the decanter and removed, while the benzene was returned to the column. The water of reaction was collected and. amounted to about 53 parts (calculated for 3 moles, 54 parts). The crude reaction products were distilled from a Claisen-type flask. The distilled products were light yellow liquids obtained in the yields indicated and having the characteristics listed in the table.

TABLE II Compounds prepared from 2-amino-2-eth Z-L3- propanediol Sa onification Nitmgen 2,4,4-Substituted-2-oxazolmcs p l (Kjeidahl), A MU d Percent B.P.,O. in em Per Cent e se Yield (mm) 2 4 4 Cale. Found Oaic. Found propionicgn Ethyl. Ethyl... Propionoxymethyl 72 143 1.015 1.446 213 192 6.57 6.61 Capric Nonyl... o Decanooxymethyl 63 200220 (l-2) 0.923 1.457 409 405 3. 42 3.59

l For the nitrogen analysis, a sample of the product was reiractionated through an all-glass helix-packed column; the main part of the material boiled at 128 0. at 10 mm.

with 2 moles of the acid indicated in the table in a reaction vessel equipped with a 3' x allglass helix packed column fitted with a decanter or separator adapted to separate two liquid layers. Benzene was added to the decanter and allowed to overflow and fill the column and just begin to drop into the reaction vessel. The mixture was heated for a period of about 10 hours over an increasing temperature range of to 240 C., during which time the Water of reaction was removed as an azeotrope with the benzene in the column. The water was separated in the decanter and removed, while the benzene was returned to the column. The water of reaction was collected and amounted. to about 53 parts (calculated for 3 moles, 54 parts). The crude reaction products were distilled from a Claisen-type flask. The distilled products were light yellow liquids obtained in the yields indicated and. having the characteristics listed in the table.

TABLE I EXAMPLE III The compounds listed in Table III were prepared by mixing 1.5 moles of the appropriate organic acid listed in the table and 0.5 mole of tris(hydroxymethyl) aminomethane in a 3'x% all-glass helix packed column equipped with a decanter or separator adapted to separate two liquid layers. Benzene was added to the decanter and allowed to fill the column and just begin to drop into the reaction vessel. The mixture was heated for a period of 6 to 10 hours over an increasing temperature range of 150 to 240 C. to remove the water as an azeotrope with benzene. The water was separated in the decanter and the benzene returned to the column. The water which was collected amounted to between about 35 and 36 parts; calculated for 2 moles, 36 parts. The crude products were vacuum distilled from a 30 Claisen-type flask, the distilled products were oily Compounds prepared from Z-amino-Z-methyl- 1,3-propanediol Nitro e 2,4,4-Substituted-2-oxazolines a ag i iggf (Kjeldgh l Acid Used I Pgriglelnt BZSBIJO. g Per Cent 2 4 4 Oalc. Found Calc. Found Benzoic Phenyl Methyl. Benzoiigymethyln 83 195-215" (2-3), 1.156 1.569 295 296 4. 75 4. 71 Oaprylic Heptyl. do. Octanooxymethyl. 76 -180" (l2) 0. 935 1.452 339 334 4.13 4. 20 Capric Nonyl do Decanooxymethyl 78 200-210 (1-2). 0.922 1.455 395 387 3.54 3. 54

1 A 5% excess 01 organic acid was used.

liquids except the one prepared from stearic acid (marked h) which was a light brown wax which was not distilled but was poured into a tray to solidify. In preparing the compound using caprylic acid (marked d), 5% excess of acid was employed. The compounds were obtained in'the yields indicated and had the characteristics listed in the table. 7

of hydrogen, alkyl and acyloxymethyl; the step which comprises heating a mixture of a primary amine polyhydroxy compound of the following formula:

HOCHr--CBEOH TABLE III Compounds prepared with tris(hydroxymethzll)- aminometha'ne v I 2, 4, 4-Substituted-2-oxazolines g l g (llgjiggggili) e u va en Add used Plignt B.( 53130. g m) q Percent 2 4 4 Cale. Found Oalc. Found Butyn'c. Propyl ButyroxymethyL. ButyroxymetliyL. 90 135-140" (2-3). 1.047 1. 453 157 158 4.47 4. 52 Gaproic Pentyl Hexa-noiixymethyl. Hexanoiixymethyl. 83 170 (2) 0.994 1.456 199 194 3.52 3.58 Caprylic Heptyl Octanoo'xymethyl. Octanolixymethyl. 87 250260 (2)-- 0.960 1.458 241 221 2.91 2.96 Stearic Heptadecyl. Stearoxymethyl. StearoxymethyL. 100 P. 76 4 48 450 1.56 1.61

1 5% excess of acid used. 2 Not distilled.

in which R is selected from the group consisting of hydrogen, alkyl, and hydroxymethyl, with a monocarboxylic acid in the proportion of one mole of monocarboxylic acid for each hydroxyl group in the primary amine polyhydroxy com pound until at least 3 mole equivalents of water product treated with additional acid to esterify have separated.

the hydroxymethyl group.

3. A process for preparing esters of 4-hydroxy- TABLE IV Compounds prepared in separate steps Nitrogen Acid Used 2, 4, 4-Substituted-2-oxazollnes i g igfiggf (Kieldahl),

Per Cent B. P., =0. n Per Cent Yield (mm.) D

1st Step 2nd Step 2 4 4 Cale. Found Cale. Found Lauric Propionic. Undecyl Methyl. Propionoxymethyl 36 1701190" (2-3) 0.943 1.452 325 330 4. 30 4.30 o.. Benzolc do do.. BenzoiixymethyL... 60 210 230 (1-2) 0.994 1.495 373 368 3.75 3.70 Benzoic Laurio PhenyL. do Lauroxymethyl 47 235 (1-2) 0.985 1.491 373 361 3.75 3.70

While the above describes the preferred embodiments of my invention, it will be understood that departures may be made therefrom within the scope of the specification and claims.

What is claimed is:

l. A process for preparing esters of 4- (hydroxymethyD-Z-uxazolines which comprises reacting a primary mono amine polyhydroxy compound, containing not in excess of three hydroxyl groups and having the hydroxyl groups on carbons adjacent the carbon carrying the amino group, with a monocarboxylic acid in the proportion of one mole of acid for each hydroxyl group of the primary amine polyhydroxy compound until at least 3 mole equivalents of water have separated.

2. In a process for forming a substituted 4- hydroxymethyl-2-oxazoline and esterifying at least one hydroxymethyl group in a single operation to form compounds having the following structure:

SE10 0 0R in which the R substituents are identical and are selected from the group consisting of alkyl and aryl, R is selected from the group consisting HOGHr--CHzOH OHIOOOR in which R is selected from the group consisting of hydrogen, alkyl, and hydroxymethyl, with a monocarboxylic acid in the proportion of one mole of acid for each hydroxyl group of the primary amine polyhydroxy compound over an increasing temperature range from about C. to about 240 C. until a quantity of water has separated equal to one mole equivalent plus an additional mole equivalent for each hydroxyl group of the primary amine polyhydroxy compound.

v a gae-gear 4. A PIOBESSE for preparing; Ze-ghenyi-tmretiiyk khenzoiixymethyl-fi-oxazoline which euntnrises heating: one. moie; ofs 2aaminoe2-methy11-L3mmrpanediol with at least two moles of benzoic acid over an increasing temperature range of about 150 C. to 240 C, until approximately three moles of water of reaction have separated.

5. A process for preparing 2-nony1-4-ethy1-4- decanoiixymethyl-Z-oxazoline which comprises heating one mole of 2-amino-2-ethy1-L3-prvpanediol with at least two moles ofieapnie-aeiti over an increasing temperature range of 150 C. to-240 C. untilapproximately threemolesof water of reaction have separated.

6% A'procesa for preparing; 2- (heptadecyl) 4,4- bis ('stearoxymethyl) 2 oxazoline which com, prises: reacting one mole of tris(hydroxymethyl) aminomethane with. three moles of, stearic acid.

over an increasing, temperature range. of. about 8; 1.50 G mzao G. unti-1-- approximateiy fiour, moles of. water of reaction; have separated.

PHILIPsEi TRYONL REFERENCES (JIEIZJ'ID The foiibwi n-g-references are of recorcf in the fil-e of this patent:

UNITED STATES PATENTS Number Name Date agzraflaa- Hodginaet a1 Sept. 17, 1940 23621736 De Groote et a1 Nov. 11, 1941 2,309,243- De Groote etal- Jan. 26-, 1943 2,368,075 Wampner Jan. 23, 1945 2,402,791 Wam-pn-er June 25, 1946 FOREIGN PATENTS Number Country Date 830,125 France May 9, 1938 

2. IN A PROCESS FOR FORMING A SUBSTITUTED 4HYDROXYMETHYL-2-OXAZOLINE AND ESTERIFYING AT LEAST ONE HYDROXYMETHYL GROUP IN A SINGLE OPERATION TO FORM COMPOUNDS HAVING THE FOLLOWING STRUCTURE: 